[00:00:53] Speaker 03:
Let me proceed.

[00:01:03] Speaker 03:
Mr. Hurst.

[00:01:04] Speaker 00:
Thank you.

[00:01:04] Speaker 00:
May it please the court, Jim Hurst on behalf of HUSPIRRA.

[00:01:08] Speaker 00:
I'm going to use my opening segment of eight minutes to address our affirmative appeal on the 071 patent.

[00:01:16] Speaker 00:
This is not the kind of case that a certificate of correction was designed to address.

[00:01:21] Speaker 00:
Cubist, in its claims, deliberately defined its claimed compound through its stereochemistry after telling the patent office during prosecution that it is important, quote, to use exact, quote, exact stereochemistry when designing compounds.

[00:01:40] Speaker 00:
Cubist could have avoided relying on stereochemistry, which they tell us now is subject to change, by using a product by process claim.

[00:01:49] Speaker 00:
But that would have given them more narrow coverage

[00:01:51] Speaker 00:
because infringement would have required using that process.

[00:01:54] Speaker 00:
So they went broad.

[00:01:56] Speaker 00:
And they deliberately defined their compound with its stereochemistry.

[00:02:02] Speaker 00:
Given that context, this is not the kind of situation that we can call a minor change.

[00:02:07] Speaker 00:
It effectively swaps one compound for another.

[00:02:11] Speaker 05:
Under the legal standard.

[00:02:12] Speaker 05:
Would it matter, in your view, if the L stereoisomer didn't exist?

[00:02:20] Speaker 05:
And the only stereoisomer found in nature or had ever been created was the de-isomer.

[00:02:25] Speaker 05:
I think as a matter of chemistry, that's probably not possible, but let's assume it is in the hypothetical world.

[00:02:30] Speaker 00:
It was an impossibility, and it was apparent to one of ordinary skill in the art.

[00:02:35] Speaker 00:
I guess, yes, I think that might make a difference if it was an apparent error, but that's not what we have here.

[00:02:40] Speaker 00:
We have a situation where the law is if you reach new territory with your corrected claim, the certificate of correction is invalid.

[00:02:50] Speaker 00:
And in this particular case, that's what we had if you look at the claims from the proper perspective.

[00:02:58] Speaker 00:
The proper perspective is you construe the original claims and you compare it to the corrected claims.

[00:03:03] Speaker 00:
What's the proper perspective?

[00:03:05] Speaker 00:
A 1987 person of ordinary skill in the art.

[00:03:09] Speaker 00:
You basically take yourself into a time machine.

[00:03:11] Speaker 00:
You go back to 87 and you say, how would one construe this claim that expressly references LASN?

[00:03:19] Speaker 00:
What that person of ordinary skill in the art would know is that you can make this claim compound one of two ways from the spec, semi-synthesis or fermentation.

[00:03:29] Speaker 00:
No, 1987, person of ordinary skill in the art would have ever imagined that that claim would reach the DASN version of this molecule made semi-synthetically.

[00:03:44] Speaker 00:
And yet, Cubis tells us in their briefs that the corrected claims

[00:03:49] Speaker 00:
cover DASN made semi-synthetically.

[00:03:53] Speaker 00:
That's new territory.

[00:03:54] Speaker 00:
That's broadening.

[00:03:56] Speaker 00:
That means the certificate of correction is incorrect, is invalid.

[00:04:00] Speaker 00:
Cubis really does offer a results-oriented analysis.

[00:04:04] Speaker 00:
Think of it this way.

[00:04:06] Speaker 00:
Say it turned out that the LASN molecule was the better antibiotic.

[00:04:12] Speaker 00:
Cubis could have stuck with his original claims and enforced them against

[00:04:17] Speaker 00:
the LASN molecule, which is justifiably so, which is expressly recited in the claims and enabled through semisynthesis.

[00:04:27] Speaker 00:
But it turned out that the DASN molecule is better, and therefore they got themselves a certificate of correction that swapped compounds to the better antibiotic.

[00:04:37] Speaker 00:
They're both antibiotics.

[00:04:37] Speaker 05:
I think they're not going to concede.

[00:04:39] Speaker 05:
I would imagine that your hypothetical would be true, because I think what they would say is, well, no, they couldn't have.

[00:04:46] Speaker 05:
the L-ASN, because they had already committed themselves to something that was widely understood to be Daptomycin, which, as it ultimately turns out, was the D-stereoisomer, not the L. And therefore, they were stuck with Daptomycin, notwithstanding the error in the structural description.

[00:05:05] Speaker 00:
Well, think of it.

[00:05:05] Speaker 00:
I think that's not correct, and this is why I say so.

[00:05:08] Speaker 00:
The only reason they're even arguing about DSAN now is because they corrected the claim.

[00:05:12] Speaker 00:
If they stuck with the original claim,

[00:05:14] Speaker 00:
What's the question?

[00:05:16] Speaker 00:
What does the claim cover?

[00:05:17] Speaker 00:
Well, it expressly covers LASN.

[00:05:19] Speaker 00:
And what's the next question?

[00:05:20] Speaker 00:
Does the SPAC enable it?

[00:05:22] Speaker 00:
It does enable it.

[00:05:23] Speaker 00:
They could have justifiably stuck with that original claim and enforced it against folks out there using LASN if it turned out to be the better antibiotic.

[00:05:32] Speaker 05:
Well, I want to beat this to death.

[00:05:40] Speaker 05:
Seems to me that you can have, in the history of chemistry, there have been a lot of mistakes as to how things actually work and what their actual structure is.

[00:05:49] Speaker 05:
Suppose somebody, just to take a really silly counterchemical example, if somebody is describing sulfuric acid and they make it very clear that they are describing what every chemist understands to be sulfuric acid, and they say, which has the structure H2SO3?

[00:06:08] Speaker 05:
It seems to me that is.

[00:06:09] Speaker 05:
As long as we know it's sulfuric acid, the fact that you've described it incorrectly is a minor mistake.

[00:06:16] Speaker 05:
It depends on the context, right?

[00:06:17] Speaker 00:
Right.

[00:06:18] Speaker 05:
But the question is, is this context one of those contexts in which it's so clear from the rest of the specification that they were claiming daptomycin, which is, as it turns out, in effect, H2SO4 or the stereoisomer, isn't that the same?

[00:06:38] Speaker 00:
No.

[00:06:39] Speaker 00:
It's the way they chose to claim their compound.

[00:06:42] Speaker 00:
This isn't sulfuric acid where it's been around forever.

[00:06:46] Speaker 00:
This is a new compound, and they had a choice.

[00:06:49] Speaker 00:
They could have said, product by process, if they had any doubts about its stereochemistry, and that would have protected them, and that would have given them more narrow coverage.

[00:06:56] Speaker 00:
They made a deliberate choice, let's go with stereochemistry.

[00:06:59] Speaker 00:
And remember the legal standard?

[00:07:01] Speaker 00:
The legal standard is how would you construe this claim back in 1987?

[00:07:06] Speaker 00:
The district court, the only way the district court construed the original claim to cover DASN is as follows.

[00:07:14] Speaker 00:
The district court said there's an ambiguity in the claims, right?

[00:07:17] Speaker 00:
He sees the reference to A21978C and says, well, that refers to the fermentation product and that must be DASN.

[00:07:26] Speaker 00:
The mistake that we believe the district court made is

[00:07:30] Speaker 00:
That's after acquired knowledge from 2001.

[00:07:33] Speaker 00:
People only learned that in 2001.

[00:07:35] Speaker 00:
Put yourself in my time machine in 1987.

[00:07:38] Speaker 00:
That claim itself teaches that LASN is in fact within the family of peptides A21978C.

[00:07:46] Speaker 00:
So that's what a person in 1987 would have concluded.

[00:07:51] Speaker 00:
It's really undisputed in the record.

[00:07:52] Speaker 00:
We asked our expert about it.

[00:07:54] Speaker 00:
There's nothing that anybody would have known in 1987 to lead them to the conclusion that that claim covered DASM.

[00:08:02] Speaker 00:
And I'm running into my rebuttal time now.

[00:08:04] Speaker 00:
So if there's any further questions.

[00:08:07] Speaker 03:
Thank you, Your Honors.

[00:08:16] Speaker 01:
Thank you, Your Honor.

[00:08:17] Speaker 01:
May it please the court.

[00:08:18] Speaker 01:
My name is Bill Lee and together with my partner, Lisa Carazzolo, I represent Cubist.

[00:08:23] Speaker 03:
Mr. Lee, let me cut to the chase where I'm interested.

[00:08:27] Speaker 03:
Sure.

[00:08:27] Speaker 03:
And that is, a couple of times, Haspera goes after you for the Orange Book delisting.

[00:08:36] Speaker 03:
Sure.

[00:08:37] Speaker 03:
Tell me why it was delisted.

[00:08:41] Speaker 01:
Absolutely, Your Honor.

[00:08:42] Speaker 01:
As Your Honor knows,

[00:08:43] Speaker 01:
The Hatch-Waxman area is what I would call a litigation-rich environment.

[00:08:48] Speaker 01:
Everybody asserts every claim that they can assert.

[00:08:51] Speaker 01:
It's patent claims, it's equitable conduct claims, it's antitrust claims, as Your Honor knows.

[00:08:58] Speaker 01:
When the error was discovered, and to be clear on one thing, to go to Judge Bryson's question, at the time this invention was made and the application was filed, the only naturally occurring compound was de-aspergy.

[00:09:12] Speaker 01:
There was no naturally occurring Ellisberry gene.

[00:09:14] Speaker 01:
There's no dispute about that.

[00:09:15] Speaker 01:
In fact, the semi-synthetic one wasn't made two years later.

[00:09:19] Speaker 01:
When we discovered in 2007, knowing that there was a lot of litigation, a lot of claims, we took the cautious step of saying, look, while it's being corrected, we've asked for it to be corrected.

[00:09:32] Speaker 01:
But until it is, we're going to take the conservative step of not listing it.

[00:09:36] Speaker 01:
As soon as it was corrected, after we went through the process with the patent office, we listed it immediately.

[00:09:41] Speaker 01:
But on this issue, Your Honor, and I will use my time to do two things.

[00:09:46] Speaker 01:
One is to address this issue, but two, to address four legal errors that the district court made that resulted in the invalidation of four patents.

[00:09:55] Speaker 01:
And to be clear, these are four patents, particularly two of them.

[00:09:59] Speaker 01:
Without these patents, there are thousands and thousands of people who never would have been as successfully treated and hundreds of lives that were saved because there was no product on the market.

[00:10:11] Speaker 01:
But let me answer on the reissue first.

[00:10:13] Speaker 01:
Here's what the district court did, and it's not quite what Mr. Hurst represented.

[00:10:18] Speaker 01:
He heard from two experts, Dr. Gerwick and Dr. Gammon.

[00:10:22] Speaker 01:
Dr. Gammon is their expert, and we would ask the court to consider his testimony that begins in A359, because he gave his opinion without ever reading the specification of the patent.

[00:10:34] Speaker 01:
Literally, without reading the specification of the patent.

[00:10:37] Speaker 01:
As a consequence,

[00:10:38] Speaker 01:
There was no rebuttal to what Dr. Gerwick said and equally important to what the district court found, which is that daptomycin, the compound, was described in four separate ways.

[00:10:51] Speaker 01:
It was described as A21978C, as Mr. Hurst said, not a term of art in the field.

[00:10:58] Speaker 01:
That distinguishes the Barrett case.

[00:11:00] Speaker 01:
It was described as LY146032, not a term of art in the field.

[00:11:08] Speaker 01:
Then, at column 7, line 41 to 60, it was described by the process by which this natural compound was made, with reference to two other pens.

[00:11:18] Speaker 01:
It's a fermentation process that results in Daptomycin.

[00:11:22] Speaker 01:
To go to Judge Bryson's question, it results in the D-asparagine.

[00:11:26] Speaker 01:
And there's no dispute about that.

[00:11:28] Speaker 01:
And then there is the structural diagram with the L-asparagine.

[00:11:31] Speaker 05:
You say the LY, I forget the numbers, 1, 5, 6, 9, was not

[00:11:38] Speaker 05:
a term used in the art, but it was at least a term used in Lilly's labs, correct, for what we now know to be the de-asparagine.

[00:11:48] Speaker 01:
Yeah.

[00:11:49] Speaker 01:
And in fact, Your Honor, it was a term used.

[00:11:51] Speaker 01:
And the specification makes this clear.

[00:11:54] Speaker 01:
In both, Mr. Hertz and I had to sort of look down to read the numbers.

[00:11:58] Speaker 01:
Both the cyclic peptide and the LY146032 are described in the specification

[00:12:07] Speaker 01:
at column 7, line 41 to 60, as a result of the fermentation process that produces the natural product.

[00:12:15] Speaker 01:
And then there is, without a doubt, there is the fourth way of describing it, which is the structural diagram.

[00:12:21] Speaker 01:
And what the district court correctly concluded is, one of ordinary skill in the art would look at the client and the pet.

[00:12:27] Speaker 01:
They would see the diagram, but they would also see the reference to the secret peptide.

[00:12:33] Speaker 01:
They would read the specification, which is what Dr. Gammon didn't do.

[00:12:37] Speaker 05:
You alluded briefly to the Bayer case.

[00:12:43] Speaker 05:
Could you expand on that?

[00:12:45] Speaker 05:
Because it seemed to me that you characterize it in your brief as being the polar opposite of this case.

[00:12:50] Speaker 05:
And it seemed to me it's a lot closer than that.

[00:12:52] Speaker 05:
It may be distinguishable, but I'd like to hear what your response to it is.

[00:12:56] Speaker 01:
I think, Your Honor, if we characterize it as a polar opposite.

[00:12:58] Speaker 05:
I may have added the word polar.

[00:13:00] Speaker 01:
I think you said opposite.

[00:13:03] Speaker 01:
We intended to describe it as distinguishable.

[00:13:05] Speaker 01:
In Bayer, they selected a word.

[00:13:07] Speaker 01:
that had a common meaning to those of ordinary skill in the art.

[00:13:11] Speaker 01:
And then, at claim construction, they tried to reverse field and say, no, that's not what we intended.

[00:13:17] Speaker 01:
The difference here is, and this is in the claim.

[00:13:20] Speaker 01:
This isn't just the LY, which is in the spec.

[00:13:22] Speaker 01:
Here, we put in A2197HC literally into the claim.

[00:13:29] Speaker 01:
And the specification tells you exactly what that is.

[00:13:32] Speaker 01:
It's the fermentation process that results from this process.

[00:13:36] Speaker 01:
There is no dispute.

[00:13:37] Speaker 01:
today that, in fact, is de-esperaging.

[00:13:40] Speaker 05:
So are you saying that if you had left out the LY and you had owned from the claim and all that had been in the claim had been the structure, then you would be on all fours with buy-in?

[00:13:50] Speaker 01:
Your Honor, I would take it in three different boxes.

[00:13:55] Speaker 01:
At the extreme, which I think is maybe the hypotope you're asking me, if all the claim referred to was the Formula 3 structure and there was nothing in the specification.

[00:14:04] Speaker 05:
No, no.

[00:14:04] Speaker 05:
The spec is loaded with indications that it's

[00:14:07] Speaker 05:
supposed to be daptomycin, but the only thing in the claim is the, because I think in Bayer that that was the situation, if I recall correctly.

[00:14:15] Speaker 01:
I think that it's close to the situation.

[00:14:17] Speaker 01:
They actually use the word in the claim.

[00:14:19] Speaker 01:
Okay.

[00:14:20] Speaker 01:
I think your honor, if we, if we take the three buckets, my three buckets would be the one that we are confronted with, which was it's in the claim and you have to go to the spec to get it defined.

[00:14:30] Speaker 01:
And I think that combination of the specification and what's in the claim is what the district court correctly relied upon.

[00:14:38] Speaker 01:
I think if you go to, I think a middle box, which may be where your honor is, which is, it's got the formula three, but everything in the spec talks about it being the result of a fermentation process.

[00:14:50] Speaker 01:
I think you would still have an issue to resolve and the district court would take testimony the way they took to determine how one of the organized skill in the art would have viewed it at the time.

[00:14:59] Speaker 01:
I think the extreme would be,

[00:15:01] Speaker 01:
Just one, go three, and nothing in the spin.

[00:15:03] Speaker 01:
And that would be a problem.

[00:15:04] Speaker 01:
That would be pretty easy.

[00:15:05] Speaker 01:
That would be a problem.

[00:15:06] Speaker 05:
But do you think Bayer is more in that category than in the middle category?

[00:15:10] Speaker 01:
No, I think the distinction between Bayer, whether polar opposite or not, I think the distinction between Bayer is the term that was focused on Bayer had a meaning to those of ordinary skill in the arpeggio.

[00:15:21] Speaker 01:
And the cyclic peptide does not.

[00:15:24] Speaker 01:
If I could turn to arpeggio and the four errors

[00:15:28] Speaker 01:
In the interest of time, let me describe what they are because they are important and they're each legal.

[00:15:35] Speaker 02:
Could I maybe direct you because it's the one that's troubling me the most and that's the obviousness finding on the high jury.

[00:15:45] Speaker 02:
This product by process stuff I find difficult, but it seems to me that the district court

[00:15:51] Speaker 02:
found that at least the purification processes were obvious, and it doesn't seem that you dispute that all that much.

[00:15:58] Speaker 02:
What you dispute, I think, is that the ultimate product obtained by those processes is not obvious.

[00:16:05] Speaker 02:
But I don't really follow that, because if, at least in these cases, it seems like

[00:16:11] Speaker 02:
it would always be obvious to try to get a more pure form of the drug.

[00:16:16] Speaker 01:
Your Honor, it might be obvious to try to get a more pure form of the drug.

[00:16:19] Speaker 01:
But let me answer your question in these two parts.

[00:16:24] Speaker 01:
And I like to address both of them.

[00:16:27] Speaker 01:
I think the second part will go most directly to Your Honor's question.

[00:16:30] Speaker 01:
Because there's an anticipation finding and an obviousness finding.

[00:16:34] Speaker 01:
And let me just say this on the anticipation finding.

[00:16:37] Speaker 01:
The anticipation finding

[00:16:39] Speaker 01:
relies upon prior art that's not prior art.

[00:16:44] Speaker 01:
I mean, literally.

[00:16:45] Speaker 01:
We have an opinion that says, I'm relying upon this whole piece of prior art 843-FET.

[00:16:52] Speaker 01:
The compounds are different.

[00:16:54] Speaker 01:
I know they're different.

[00:16:56] Speaker 01:
So what am I gonna do?

[00:16:57] Speaker 01:
I'm gonna rely upon these clinical trial life plots with no provenance, no one knows where they came from, how they were made.

[00:17:04] Speaker 05:
And we don't have any indication that that

[00:17:08] Speaker 05:
chemical was the lily 43 that was produced by the 484 process.

[00:17:16] Speaker 01:
There was no evidence it was produced by the 843.

[00:17:19] Speaker 01:
In fact, Your Honor, there are a lot of numbers flying around.

[00:17:23] Speaker 01:
There's no evidence that's made by the 843.

[00:17:26] Speaker 01:
And probably, I think, to go to part of Judge Hughes' question, because they're related, Your Honor, the lots, actually, if you go to and recite it to you, literally,

[00:17:37] Speaker 01:
the record says, we don't know how these lots were made.

[00:17:41] Speaker 01:
I mean, literally, that's what's in the NDA to the FDA.

[00:17:45] Speaker 01:
So what happened is there was a hole, and there was a hole because the products that are made by the 843 patent are different than the products made by the process claims.

[00:17:57] Speaker 01:
And I start there, Your Honor, because you're related.

[00:17:59] Speaker 01:
So if you start with that fact, and in fact, the district court found that the products made by the 843 patent are different

[00:18:08] Speaker 02:
So just, I think you're going where I want, but to clarify, I assume I agree with you that that anticipation finding is not correct because it doesn't cover everything.

[00:18:17] Speaker 02:
Right.

[00:18:17] Speaker 02:
What do you need, what would you need to add to 843 patents to get to your patent?

[00:18:24] Speaker 01:
Well, Your Honor, to get to the Hyperion patents, I think this would be the analytical framework.

[00:18:30] Speaker 01:
First, there's a question, since they're product by process claims, are the products different?

[00:18:35] Speaker 01:
And the district court of death found that they were.

[00:18:38] Speaker 01:
He found that the patent itself said, as to endotoxins, they're different.

[00:18:42] Speaker 01:
He found, as a matter of fact, that... Okay, I think I see this.

[00:18:45] Speaker 02:
So, again, the 843 patents produce a different product.

[00:18:52] Speaker 02:
We can start with that.

[00:18:53] Speaker 02:
But if it's obvious to add in this other purification process that will get you to your product, why isn't that still a sufficient obviousness finding?

[00:19:04] Speaker 01:
Your Honor, there are three reasons.

[00:19:07] Speaker 01:
And the first is this.

[00:19:09] Speaker 01:
It has to be a combination of, and we don't concede that the implementation was quite as common as they say, but you have to, the analytical framework requires that you combine them to get what is claimed.

[00:19:24] Speaker 01:
Not just say A was out there, B was out there, to get what was claimed.

[00:19:29] Speaker 01:
So if I could give your honor, I think one that will help answer the question or frame a question.

[00:19:33] Speaker 01:
Consider claim 187 of the high peer dependence.

[00:19:37] Speaker 01:
It claims 97% purity.

[00:19:41] Speaker 01:
You will search the district court's opinion in vain to find anything that says, take A, take B. Take my cell aggregation and take ion exchange chromatography.

[00:19:52] Speaker 01:
Combine them, and there's a reasonable expectation that you get to 97.

[00:19:57] Speaker 01:
Now, Your Honor, that's the difference I tried to make at the outset between, yeah, you'd also like to get more pure.

[00:20:04] Speaker 01:
That's not the question.

[00:20:05] Speaker 01:
The question is, do we have a reasonable expectation of getting there?

[00:20:08] Speaker 01:
And the problems, the three boxes I was going to try to put this in, the products are different.

[00:20:13] Speaker 01:
So if I take that and set it aside, now you have these two purification processes.

[00:20:19] Speaker 01:
And the reason we don't even can see there is if you look at what the district court did, it said, well, myself, you know, filtration was known.

[00:20:30] Speaker 01:
Then there's a problem.

[00:20:32] Speaker 01:
because you get to the ion exchange chromatography and the prior art they're looking at is the 843 patent.

[00:20:38] Speaker 01:
And the 843 patent says, ion exchange chromatography for Gapdomycin is a bad idea.

[00:20:45] Speaker 01:
So what does the district court rely upon to reach the obviousness determination?

[00:20:50] Speaker 01:
It relies upon the disclosure of the patent.

[00:20:53] Speaker 01:
So what you have is, you have setting aside anticipation, you have the foundation

[00:20:59] Speaker 01:
of the opposite inquiry, which is the products are different.

[00:21:03] Speaker 01:
You then have a real question of whether there's a legal error, because taking the two techniques, whether the district court, in fact, used the patent itself to supply the information on the second, then you have... So you know you're well into your rebuttal time.

[00:21:23] Speaker 01:
Let me just add one sentence and... Whatever you want.

[00:21:28] Speaker 01:
I'm not going to give a lot.

[00:21:30] Speaker 01:
Let me just add one sentence.

[00:21:33] Speaker 01:
On the dosing sentence, two sentences.

[00:21:38] Speaker 01:
One is, it's very important that you read the reference as a whole.

[00:21:43] Speaker 01:
And the reference is Woodworth.

[00:21:46] Speaker 01:
And the reference says nothing about dosing interval.

[00:21:49] Speaker 01:
It says nothing about skeletal muscle toxicity.

[00:21:52] Speaker 01:
And the most critical fact is there are a group of doses that are disclosed.

[00:21:57] Speaker 01:
Those doses, in fact, in fact, as a matter of what occurred, those doses were what caused the skeletal muscle toxicity issue that led to the product being taken off the market.

[00:22:10] Speaker 01:
I'll reserve the last minute if I could, Your Honor.

[00:22:12] Speaker 00:
Let me just quickly address some questions from the 071 patent.

[00:22:20] Speaker 00:
Judge Wallach, to address your question, under the law, the only reason that patent should have been removed

[00:22:25] Speaker 00:
from the orange book is if it did not cover the DASN molecule and it was removed.

[00:22:31] Speaker 00:
Second, Judge Bryson, in response to one of your questions, I think Mr. Lee pointed out that the LASN molecule is not naturally occurring.

[00:22:40] Speaker 00:
The claims are not limited to naturally occurring antibiotics.

[00:22:43] Speaker 00:
In fact, if you look at the claim itself, it is a pure, here's the structure of the compound that we are now claiming.

[00:22:51] Speaker 00:
And basically, the argument is let's

[00:22:55] Speaker 00:
let's convert that compound claim into a product by process claim.

[00:22:59] Speaker 00:
They could have done that before.

[00:23:00] Speaker 00:
It would have limited the scope of their patent coverage.

[00:23:03] Speaker 05:
I think what he was responding to was that at that time, for all practical purposes, this case was like my hypothetical case in which the second recited, the actually recited structure didn't exist.

[00:23:19] Speaker 05:
Well, that's not true.

[00:23:19] Speaker 05:
That's not true at all.

[00:23:21] Speaker 05:
It didn't exist at that time.

[00:23:22] Speaker 05:
I mean, it was possible to create it, but it didn't exist.

[00:23:25] Speaker 00:
No different than any other patented claims compounds where the compounds are enabled and this one was enabled through semi-synthesis and it was claimed as a stereoisomer.

[00:23:35] Speaker 00:
The question is,

[00:23:37] Speaker 00:
How would someone have reviewed this claim in 1987?

[00:23:40] Speaker 00:
You have to apply Markman principles to look at the original claim and compare it to the next claim.

[00:23:46] Speaker 00:
How do you get in 1987, when you look at this particular compound, it's written out of the structure.

[00:23:54] Speaker 00:
How do you, as a judge, say, you know what?

[00:23:56] Speaker 00:
I think I'm going to replace the L with a D. In 1987, you would never have done that.

[00:24:01] Speaker 00:
And that invalidates the certificate.

[00:24:06] Speaker 00:
The only reference in the claim, your honor, to anything that supports the notion that this would be unknowingly DASN is this reference to A21978C, which is talked about as a fermentation product.

[00:24:21] Speaker 00:
But your honor, back in 1987.

[00:24:23] Speaker 00:
Remember, you're limited to the patent record.

[00:24:25] Speaker 00:
You're not going into Eli Lilly's notebooks in the laboratory.

[00:24:28] Speaker 00:
You're not looking at clinical trials and what they're actually physically giving.

[00:24:32] Speaker 00:
You're looking at the patent record.

[00:24:34] Speaker 00:
And that reference to the family of cyclic peptides, that would have included LASN to any person of ordinary skill in the art as of 1987, when we go back in our time machine.

[00:24:46] Speaker 00:
Let me address the purity patents.

[00:24:50] Speaker 00:
Mr. Lee is re-arguing the facts.

[00:24:54] Speaker 00:
The district court, these are product by process claims.

[00:24:58] Speaker 00:
The district court found unchallenged finding that the underlying processes were obvious.

[00:25:06] Speaker 02:
Where's the finding that the actual product claims are obvious, that the specific purity levels claimed by the various claims?

[00:25:15] Speaker 02:
Because I don't find that.

[00:25:17] Speaker 02:
It seems to me that it may follow somewhat logically that

[00:25:21] Speaker 02:
If you apply obvious purification principles to this, you get better product.

[00:25:28] Speaker 02:
But doesn't our case law actually require that the products themselves be obvious?

[00:25:34] Speaker 00:
The district court was addressing the argument that QIS made.

[00:25:37] Speaker 00:
QIS below said the reason my patents aren't valid is not because I got higher purity.

[00:25:43] Speaker 00:
If the ion exchange column is obvious and micelle filtration is obvious,

[00:25:50] Speaker 00:
both designed to increase purity, and the record included evidence that if you want to get high purity, all you do is run the material multiple times.

[00:25:58] Speaker 02:
But doesn't the law still require that they find that the products claimed and their specific purity levels be obvious?

[00:26:07] Speaker 00:
That is exactly what the district court did find.

[00:26:09] Speaker 00:
But remember, this is Cubist argument.

[00:26:11] Speaker 00:
Cubist argued that the reason my patent is valid is because I produced structurally and functionally different material.

[00:26:20] Speaker 00:
The district court rejected that.

[00:26:22] Speaker 00:
I think that your conversation with Mr. Lee suggested that there was a belief that it was different, that products were different.

[00:26:27] Speaker 00:
Here's what the district court found on page 839.

[00:26:31] Speaker 00:
Dapto-Myerson compositions purified pursuant to the claim 98 process limitations, that's my self filtration, are not structurally and functionally different from those taught by the 843 patent.

[00:26:43] Speaker 00:
Okay.

[00:26:43] Speaker 00:
So he literally found there's no structural and functional difference.

[00:26:47] Speaker 00:
Next.

[00:26:48] Speaker 00:
The district court, here's what happens.

[00:26:51] Speaker 00:
Cubist has their material.

[00:26:52] Speaker 00:
They take the prior art material from the 843 Lilly patent.

[00:26:57] Speaker 00:
They send it out to an outside agency, an outside company, to do what that company always does, which is to purify proteins.

[00:27:05] Speaker 00:
You know what that company did?

[00:27:07] Speaker 00:
According to Mr. Lynch, the inventor himself, we just applied our standard process.

[00:27:12] Speaker 00:
And they ran it through an ion exchange column once.

[00:27:16] Speaker 00:
Judge Sleet found the use of an ion exchange column

[00:27:18] Speaker 00:
is obvious.

[00:27:20] Speaker 00:
He found that.

[00:27:20] Speaker 00:
It's not even challenged.

[00:27:22] Speaker 00:
By running the prior art material through a deemed obvious ion exchange column once through an outside company that does this for a living, where the inventor said, I use my standard processes, the resulting material matches every limitation.

[00:27:35] Speaker 02:
But where is the prior art that said, if you use 843 in combination with these methods, you will get purity levels of 95% and 97%?

[00:27:46] Speaker 00:
The prior art, for instance, a beginner's textbook at A332122 says, you normally get complete purification of proteins in a short period of time.

[00:28:01] Speaker 00:
And you apply the standard tools to do that.

[00:28:03] Speaker 00:
Your Honor, the expectation is that these tools do what they're supposed to do.

[00:28:10] Speaker 00:
221-22.

[00:28:11] Speaker 00:
That's the beginner's textbook that says you normally get complete purification.

[00:28:20] Speaker 02:
But what does complete purification mean?

[00:28:23] Speaker 02:
Does it mean 93% or does it mean 95%?

[00:28:25] Speaker 02:
Does it mean 100%?

[00:28:29] Speaker 00:
Complete purification means, for all intents and purposes, you have the protein with some minor amounts of impurities.

[00:28:35] Speaker 00:
Remember, it's only 97%.

[00:28:36] Speaker 00:
It's not even a particularly high level that we're talking about here.

[00:28:39] Speaker 00:
You have to give judges address the issues the other side raised Mr. Lee down below never argued you can look at the record.

[00:28:48] Speaker 00:
You can look at his sites He never said, you know where my case lies I don't think there was a reasonable expectation that you'd get up to 97% never that wasn't the issue the sole focus where they tried to save their patent was These my process creates a structurally and functionally different material

[00:29:06] Speaker 00:
And the district court in an unchallenged factual finding rejected that.

[00:29:09] Speaker 05:
And that's mainly by virtue of the endotoxins.

[00:29:12] Speaker 05:
Say again?

[00:29:13] Speaker 05:
Mostly by virtue of the endotoxins, I take it.

[00:29:16] Speaker 05:
That what?

[00:29:17] Speaker 05:
I'm missing the question.

[00:29:18] Speaker 05:
I mean, the argument was that the patents managed to eliminate endotoxins and the prior art

[00:29:28] Speaker 05:
They said both suponins and endotoxins.

[00:29:31] Speaker 05:
Yes, but 843 takes care of the suponins, right?

[00:29:34] Speaker 00:
Yes.

[00:29:35] Speaker 05:
So we're left with endotoxins.

[00:29:36] Speaker 00:
And companies have been, this is their expert witness, companies have been removing endotoxins for decades.

[00:29:42] Speaker 00:
That's A, 1053 to 54.

[00:29:45] Speaker 00:
That's a very standard thing you do with proteins.

[00:29:47] Speaker 00:
You eliminate the endotoxins and Judge Sleet specifically found, you can do that with an ion exchange column.

[00:29:53] Speaker 00:
If you look at

[00:29:57] Speaker 05:
Did you say you eliminate endotoxins with ion exchange, or endotoxins with micelle filtration?

[00:30:05] Speaker 05:
I think the, well, you could probably do it.

[00:30:08] Speaker 05:
I thought the ion exchange would not work with endotoxins.

[00:30:13] Speaker 05:
It was the micelle filtration, right?

[00:30:15] Speaker 00:
You know, something I think actually both might work, and I'm not entirely positive about that, because micelle filtration should work because it's size excluded both ways.

[00:30:23] Speaker 00:
Size filtration is supposed to work.

[00:30:24] Speaker 00:
Here's the actual finding.

[00:30:26] Speaker 00:
Even if one skilled in the art would have had to optimize other parameters.

[00:30:30] Speaker 00:
Whoops.

[00:30:32] Speaker 03:
Mr. Hirsch, you're going to have to wrap up.

[00:30:34] Speaker 00:
Can I read the last quote?

[00:30:35] Speaker 00:
Of course.

[00:30:36] Speaker 00:
Supponents could be removed using micelle filtration, which the court found obvious, as claimed in the purity patents, or using the process taught by the 843 patent prior art.

[00:30:46] Speaker 00:
After removing opponents, and that was the whole point of the 843 patent, one skilled in the art could apply the well-known ion exchange purification technique

[00:30:54] Speaker 00:
The purity patents do not claim anything other than this simple concept.

[00:31:00] Speaker 00:
And we know that when you run it through once, you get material that meets each and every claim limitation.

[00:31:06] Speaker 00:
That was undisputed.

[00:31:09] Speaker 00:
I'm over.

[00:31:11] Speaker 00:
Thank you, Your Honor.

[00:31:13] Speaker 01:
Give Mr. Lee an extra minute.

[00:31:15] Speaker 01:
In my couple minutes, three points.

[00:31:18] Speaker 01:
Judge Hughes, to go to your question, if you look at page A4048 of the appendix,

[00:31:24] Speaker 01:
You will find, actually in the pages surrounding it, you will find, contrary to what Mr. Hurst just said, we specifically address the 187 claim.

[00:31:33] Speaker 01:
We specifically said that there was nothing that would show a combination of the prior references getting to 97%.

[00:31:40] Speaker 01:
We asked for that finding.

[00:31:41] Speaker 01:
That finding was never made one way or another.

[00:31:43] Speaker 01:
And as I said before, you could search the record forever and you won't find a claim by claim analysis.

[00:31:48] Speaker 01:
And at pages A407 to A409,

[00:31:53] Speaker 01:
You'll see we asked for the claim by claim.

[00:31:55] Speaker 01:
Second point, to go to Judge Bryson's question.

[00:31:58] Speaker 01:
Actually, Judge Bryson, I don't think that, I think where we would quarrel, I don't think the 843 takes care of saponin approval.

[00:32:05] Speaker 01:
If you look at... I thought you would disagree.

[00:32:08] Speaker 01:
Well, this is a place where I'm going to marry the district court judge.

[00:32:11] Speaker 01:
At 840, he says that claim 98 provided for even better saponin removal than the process of the 843.

[00:32:20] Speaker 01:
So the patents themselves, the high-peri patents, say, we do better at endotoxins.

[00:32:24] Speaker 01:
Here's the data.

[00:32:25] Speaker 01:
And the district court found that sapinins, they did better.

[00:32:30] Speaker 05:
But nonetheless, the district, if I recall, the district court said, well, basically, the problem of the sapinins was sufficiently solved by the 843 that you could then do ion exchange chromatography and then reduce the purification.

[00:32:44] Speaker 05:
You get the purification with respect to the analogs.

[00:32:48] Speaker 01:
Yeah, you heard your honor, but then this is a place, and I'm not retrying the case.

[00:32:52] Speaker 01:
I'm focusing on legal errors.

[00:32:54] Speaker 01:
And what he did to reach that conclusion is he relied upon the disclosure at the pen.

[00:32:59] Speaker 01:
I mean, you cannot find a hole for ion exchange chromatography.

[00:33:02] Speaker 01:
He said, I'm going to fill it in by referring to the spec.

[00:33:06] Speaker 01:
Last point in the 20 seconds that remain on Woodworth.

[00:33:11] Speaker 01:
The invention here was not about dosing.

[00:33:13] Speaker 01:
It was about interval.

[00:33:15] Speaker 01:
That was the key.

[00:33:16] Speaker 01:
There's nothing in Woodworth about interval.

[00:33:19] Speaker 01:
The invention was about multiple skeletal toxicity.

[00:33:23] Speaker 01:
Nothing in Woodworth about it.

[00:33:25] Speaker 01:
Talks about once daily.

[00:33:26] Speaker 01:
Sure.

[00:33:26] Speaker 01:
Several times.

[00:33:27] Speaker 01:
Well, no, Your Honor, actually, this is where it's important to read it.

[00:33:29] Speaker 01:
What it says at the end, it says four to six milligrams per kilogram without the day.

[00:33:36] Speaker 01:
Then the sentence that follows two after that says, and divided doses given the extended half-life is the right way to go.

[00:33:44] Speaker 01:
And then if you go back to the beginning.

[00:33:46] Speaker 01:
That's right.

[00:33:46] Speaker 01:
It does say 4 to 6 milligrams per kilogram per day, possibly in divided doses.

[00:33:52] Speaker 01:
The real question is, you now have this universe.

[00:33:55] Speaker 01:
You have a group, genus, whatever you want to call it.

[00:33:58] Speaker 01:
Some of them, actually the majority of them, as the evidence shows, cause the problem.

[00:34:06] Speaker 01:
Some of them don't.

[00:34:07] Speaker 01:
No one had any idea which they were.

[00:34:09] Speaker 01:
Eight years later, someone figured it out.

[00:34:12] Speaker 01:
Thank you.